(1) Field of the Invention
This invention relates to detecting perturbation, and more particularly to a method, an apparatus and a computer programme for detecting perturbation of a physical system's state from a reference state. A useful application of this invention is to detection of perturbation of the state of a sensitive detection system such as a porous silicon biosensor by an optical technique.
(2) Description of the Art
Porous silicon is known to be suitable for fabrication into sensitive detectors. The nature of porous silicon allows a ready response at a microscopic level to perturbations caused by environmental changes. Moreover, porous silicon lends itself to interferometric techniques: well-resolved Fabry-Perot fringes may be generated on illumination of a layer of the material providing a basis for sensitive interferometric detection of its microscopic response. The response may simply be absorption or trapping of molecules in the pores of the silicon or it may be made more specific by grafting a recognition agent to an internal surface of the pores. In either case, any molecular event occurring within a porous silicon layer will affect the layer's optical properties, resulting in a change in an interference fringe pattern which can be detected and quantified if of sufficient magnitude.
Sailor et al. in WO99/12305 describe a porous silicon-based biosensor. Biosensors in general consist of two components: a recognition agent which reacts to produce a molecular or chemical signal in the presence of a specific reagent and a signal transducer which converts the molecular recognition event into a quantifiable signal. The recognition agent used in a porous silicon biosensor may be, for example, an antibody grafted into the layer and so a molecular reaction will occur in the presence of a specific antigen. Occurrence of such a reaction is observed via an optical interference pattern.
In any periodic interference pattern, such as produced by the biosensor described in WO99/12305, the separation between peaks is proportional to the optical path difference between alternative routes taken to a detector as the incident beam is partially reflected at interfaces. Under such circumstances, an accepted analysis technique is to locate peaks in the Fourier transform spectrum of the interference pattern. The location of such peak(s) provides an indication of fringe spacing(s) in the original pattern, from which a value for optical path difference can be derived. As will be described in more detail later, the interference pattern developed using a porous silicon biosensor is collected as a discrete set of spectral data points. One of the standard fast Fourier transform (FFT) algorithms is therefore used as the basis for Fourier analysis. The details of such an approach to analysing signals from a porous silicon biosensor are described by Janshoff A. et al. in J. Am. Chem. Soc. 120 pp 12 108-12 116 (1998). There are however various drawbacks to using this method of analysis, particularly in situations such as provided by the porous silicon biosensor in which the monitored binding event is capable of highly sensitive discrimination. Although the Fourier transform method per se (i.e. finding the position of the peak in amplitude of the Fourier transform of the data) is known to be optimal in locating the frequency of a single tone in white noise, many actually measured signals do not sufficiently approach this ideal and so do not allow full exploitation of the method's capabilities. Moreover, use of the FFT in particular involves interpolation in the transform spectrum between regular sampling points. This severely limits the accuracy with which a peak in the transform can be located.
There is generally a need for increased sensitivity in any detection system, and this can be achieved either by rendering a detecting medium more responsive to events to be detected or by improving extraction of required data from an inevitably-noisy experimentally detected signal. More sensitive biosensors will aid, for example, early detection of a disease antigen or rapid detection of the presence of explosives. It is an object of the present invention to provide an alternative form of perturbation detection.